Hyperinfective strongyloidiasis in the medical ward: review of 27 cases in 5 years.

ABSTRACT

Background. Hyperinfective strongyloicliasis is rare, but the mortality rate is very high. It occurs most commonly in immunocompromised patients. We reviewed the clinical presentation and mortality rate of cases managed in our facility.

Method. Twenty-seven patients with hyperinfective strongyloidiasis admitted to our medical ward over a 5-year period were prospectively studied.

Results. In our study, there were 18 males and 9 females (mean age, 58 years). Weight loss, gastrointestinal symptoms, hypoproteinemia, and anemia were the main clinical presentations. Mortality rate was 26%; human T-lymphotropic virus (HTLV-1) infection, chronic alcoholism, eosinopenia, sepsis, and prerenal azotemia on admission were poor prognostic factors. HTLV-1 infection was the main underlying disease in 71% of patients, and 44% of patients had a history of chronic alcoholism.

Conclusion. Early diagnosis and treatment with thiabendazole may reduce mortality in hyperinfective strongyloidiasis. Hyperinfective strongyloidiasis may also be a clinical marker of HTLV-1 infection in areas where both entities are endemic or in immigrants from such areas.

**********

STRONGYLOIDIASIS is an intestinal parasitic disease usually caused by the nematode Strongyloides stercoralis, and rarely caused by Strongyloides fuelleborni. These nematodes are found worldwide, but they are endemic in some parts of the world, especially in Africa, the West Indies, Southeast Asia, South America (particularly in Brazil and Colombia), Bangladesh, and Pakistan. It may infect up to 35% of some tropical populations. (1) In Dominica, West Indies, Strongyloides larvae were present in 3.7% to 5.3% of stool specimens analyzed in the laboratory using a non-concentrated technique. (2) In the United States, immigrants from the endemic areas, travelers and veterans returning from endemic areas, institutionalized individuals, and people from the Southeastern states are at risk. (3,4)

The adult worm resides in the mucosa of the small intestine, where it may exist for years, causing no symptoms or only occasional mild gastrointestinal symptoms. Overwhelming parasitemia may occur in immunocompromised patients due to repeated autoinfection and may cause hyperinfective and invasive strongyloidiasis. Although rare, this disease has a very high mortality rate. Hyperinfective strongyloidiasis occurred in 1.5% to 2.5% of patients reviewed by Milder et al (4); the mortality rate was 86% among 89 cases reviewed by Igra-Siegman et al (5); and only 1 of the 7 cases reported by Leelarasamee et al (6) survived.

The disseminated form of S stercoralis has a protean manifestation and may affect almost all the organs of the body, especially the gastrointestinal tract, lung, central nervous system, liver and biliary tract, pancreas, genitourinary tract, and joints. Gastrointestinal symptoms are the most frequent sign. (5) In an earlier study by Grell et al, (2) five patients in Dominica presented with malabsorption associated with wasting and hypoproteinemia. Rarer manifestations include meningitis, (5,7,8) eosinophilic pleural effusion, (9,10) nephrotic syndrome, (11-13) severe intra-alveolar hemorrhage, (14) adult respiratory distress syndrome, (15) severe gastrointestinal hemorrhage, (16) and reactive arthritis. (17,18) Enteric gram-negative septicemia is a common complication and an important cause of death. (57)

Various immunocompromised states, due to disease or immunosuppressive therapy, predispose patients to a hyperinfective state. Such conditions include steroid therapy. (5-7,19,20) immunosuppressive treatment in transplant recipients, (21,22) hematologic malignances, (23) human T-lymphotropic virus (HTLV-1) infection, (24-26) AIDS, (27-29) malnutrition, (30) diabetes mellitus, (30) chronic renal failure, (31,32) and alcoholic liver cirrhosis. (33)

There are many case reports of hyperinfective strongyloidiasis in the literature, but we present a series of 27 prospectively reviewed cases seen in Dominica, West Indies. This study emphasizes early diagnosis by identifying both common and unusual presentations, the underlying predisposing diseases in Dominica, and factors contributing to mortality.

METHODS

Twenty-seven cases of hyperinfective strongyloidiasis treated in the medical ward of the Princess Margaret Hospital, Roseau, Commonwealth of Dominica, West Indies between January 1995 and December 1999 were prospectively studied. The 200-bed hospital is the main referral center on Dominica, serving a population of 75,000. The aim of the study was to identify the distribution of the various clinical presentations, the mortality rate, factors influencing mortality rate, and the diseases predisposing patients to hyperinfective presentation.

Diagnosis was based on initial clinical suspicion and confirmed by microscopic examination of unconcentrated stool specimens for Strongyloides larvae. A detailed history was taken and physical examination performed on each patient with a confirmed strongyloidiasis. Further laboratory testing included complete blood count, tests for blood glucose, total protein, albumin, electrolyte, and urea levels stool occult blood test, liver function test, and chest x-ray. Blood cultures were done when sepsis was suspected.

Screening for human immunodeficiency virus (HIV-1 and HIV-2) and HTLV-1 was done by enzyme-linked immunosorbent assay (ELISA) method; all positive results were confirmed by Western blot test. All patients were admitted and treated with thiabendazole, 25 mg/kg BID for 5 days. Intravenous antiobiotic therapy, consisting of gentamicin and either ampicillin or cefotaxime, was used for sepsis. Fluid therapy and electrolyte replacement were instituted as necessary.

RESULTS

Twenty-seven patients with hyperinfective strongyloidiasis were studied. There were 18 males (67%) and 9 females (33%). The male to female ratio was 2:1. The age range was 26 to 91 years (mean age, 58 years).

Clinical Presentation

Progressive weight loss occurred in 19 patients (70%). Gastrointestinal tract symptoms occurred in 21 patients (78%); of those, 13 patients (48%) had diarrhea, 11 (41%) had abdominal pain, and 10 (37%) presented with vomiting. Hypoproteinemia/hypoalbuminemia was present in 18 patients (67%). Stool samples were positive for occult blood in 15 patients (56%). Recurrent bronchopneumonia occurred in 3 patients (11%), and an asthma-like illness was seen in 1 patient (4%). Anemia, with hemoglobin <10 g/dL, occurred in 17 patients (63%), and 8 patients (33%) had elevated blood urea nitrogen (BUN) and creatinine levels. Fever and leukocytosis were seen in 7 patients (26%). One patient (4%) had polyarthropathy involving the knee joint and finger joints, and 1 patient (4%) had a pleural effusion (Tables 1 and 2). Eosinophilia of more than 5% occurred in 8 patients (30%).

Underlying Disease

Twenty-four patients were tested for HTLV-1; of these, 17 (71%) had positive test results. All 27 patients were tested for HIV-1 and HIV-2, and all test results were negative. Twelve patients (44%) had a history of chronic alcoholism; 1 of these had a fatty liver and one had alcoholic liver cirrhosis. Of the 12 patients with chronic alcoholism, 3 had positive HTLV-1 test results. One patient (4%) who had gastric cancer and 2 (8%) patients who had non-Hodgkin's lymphoma (NHL) also had positive HTLV-1 test results (Table 3).

Mortality

The mortality rate in this study was 26%. Seven of the 27 patients in this study died while hospitalized for strongyloidiasis; 6 of those who died had tested positive for HTLV-1. Three of the patients who died had chronic alcoholism; 2 of those also tested positive for HTLV-1. The 2 patients with HTLV-1 infection and chronic alcoholism had 0% eosinophilia (Table 4). Four (57%) deaths were attributable to sepsis; blood cultures from 2 of these 4 patients grew Klebsiella pneumoniae and 1 of the 4 patients had a subdiaphragmatic pyogenic abscess discovered at postmortem examination. All 4 patients with sepsis had elevated BUN and creatinine levels. NHL and gastric carcinoma were the cause of death in 2 patients. Another patient, who also tested positive for HTLV-1 infection, had severe anemia.

DISCUSSION

The male to female ratio in this study was 2:1. Other studies have supported male predominance in strongyloidiasis. (4,5,34) Agriculture is the main occupation of the men in Dominica, and this predisposes them to Strongyloides infection. Igra-Siegman et al (5) considered the epidemiologic pattern of the underlying diseases as a factor in the sex distribution.

Clinical Presentation

Progressive weight loss was the single most common presenting symptom, occurring in 70% of patients. This could mimic malnutrition in the developing world, where parasites and malnutrition contribute significantly to diseases. Malnutrition occurring from overwhelming parasitemia may further depress the immune system, predisposing patients to further tissue invasion. Hypoproteinemia/hypoalbuminemia occurred in 67% of patients. Patients with unexplained hypoproteinemia in endemic areas, especially in the tropics, should be thoroughly screened for Strongybides infection.

Gastrointestinal tract symptoms occurred in 78% of patients, with diarrhea, abdominal pain, and vomiting being the most common symptoms. Wasting with gastrointestinal symptoms may easily be confused with gastric or colonic cancer. Gastrointestinal tract hemorrhage occurred in 6 patients (22%), and stool samples were positive for occult blood in 15 patients (56%). Diagnosis was made using endoscopy with microscopic study of duodenal aspirate. In the tropics, analysis of duodenal aspirates from gastroduodenoscopy for epigastric pain should include microscopic examination to look for Strongyloides larvae.

One patient had an asthma-like illness with recurrent wheeze, and 3 patients presented with recurrent bronchopneumonia. Asthmatic patients in the tropics who do not respond to conventional steroid therapy should have repeated stool examinations for Strongyloides, because a hypersensitivity reaction to migrating larvae may induce bronchospasm.

Eosinophilia may be absent in hyperinfective strongyloidiasis. (5) Only 30% of patients in our series had peripheral blood eosinophilia (eosinophils >5%). More severe cases were associated with eosinopenia. Anemia occurred in 17 patients (63%). This may be a consequence of gastrointestinal tract blood loss and hypoproteinemia.

One female patient had symmetrical polyarthropathy involving the knee, elbow, and finger joints, which limited her mobility. Connective-tissue screening for lupus erythematosus cells, antinuclear antibodies, and rheumatoid factors were negative. Erythrocyte sedimentation rate (ESR) was persistently elevated and her symptoms did not respond to non-steroidal anti-inflammatory drugs (NSAIDs). Stool assessment revealed Strongyloides larvae. Polyarthropathy resolved after treatment with thiabendazole. In the tropics, reactive arthritis caused by Strongyloides should be considered in seronegative arthritis unresponsive to NSAIDs. None of our patients had a cutaneous manifestation of strongyloidiasis.

Underlying Disease

Infection with HTLV-1 was the predominant underlying disease in this series. It occurred in 17 (71%) of 24 patients assessed for HTLV-1 infection. Our series supports others documented in the literature that found strong associations between HTLV-1 infection and hyperinfective strongyloidiasis. (24-26) None of our patients tested positive for HIV. Hyperinfective strongyloidiasis should be considered as a disease marker for HTLV-1 infection in areas where both conditions are endemic and in immigrants from such areas. The immunomodulatory effect of HTLV-1 infection is considered to predispose patients to hyperinfective strongyloidiasis. (26) Patients infected with Strongyloides develop a specific immunoglobulin E (IgE) response to the invasive filariform larvae. (35,36) The IgE level has been found to be low in HTLV-1 carriers and significantly lower in HTLV-1 carriers infected with Strongyloides species. (34)

Several case reports of fatal strongyloidiasis following steroid therapy are documented (5-7,19,20); however, none of our patients had undergone steroid therapy or other immunosuppressive treatment. The molting of S stercoralis rhabditiform larvae into filariform larvae, with a subsequent increase in number of parasites per host and anatomic dissemination, was proposed by Genta as a possible trigger. (37)

Twelve of the 27 patients (44%) had a history of chronic alcoholism; of those, 1 had a fatty liver and one had alcoholic liver cirrhosis. Although HTLV-1 was present in 3 of the patients, alcoholism was an independent factor in 9 (33%) of the 27 patients. In our series, chronic alcoholism and HTLV-1 infection were both underlying disorders in hyperinfective strongyloidiasis. Gaburri et al (33) found S stercoralis in 40.2% of patients in Brazil with alcoholic cirrhosis. They suggested that hepatic cirrhosis must be included as a risk factor for S stercoralis infection. Possible factors contributing to the correlation between strongyloidiasis and alcoholism include malnutrition and chronic liver disease, in addition to suppression of hematopoiesis by alcohol. Further studies are needed to determine the causal relationship between alcoholism and hyperinfective strongyloidiasis.

MORTALITY

In various reports in the literature, the mortality rate is very high in hyperinfective and invasive strongyloidiasis. (5-7) In this series, the mortality rate during hospitalization of the 27 patients treated for strongyloidiasis at our institution over a 5-year period was 26%. Early diagnosis was made in all cases, and thiabendazole therapy instituted immediately. This might be an important factor in the low mortality rate in this series. Four (57%) of the 7 patients who died had evidence of sepsis. Sepsis is a major contributor to mortality in most cases. (5-7) All 4 patients with sepsis also had elevated BUN and creatinine levels on admission. Sepsis and prerenal azotemia, especially on admission, are considered to be poor prognostic signs in our series. Dehydration from diarrhea and vomiting may also contribute to the azotemia. The mechanism of infection with gram-negative enteric organisms in sepsis associated with strongyloidiasis is not well understood. Some authors have considered the dissemination of the organism from the gastrointestinal tract during the migration of invasive filariform larvae as a possible cause. (38) Patients with unexplained gram-negative septicemia in endemic areas should be thoroughly screened for Strongyloides species.

Peripheral blood eosinophilia occurs in uncomplicated strongyloidiasis, but eosinopenia is associated with a poor clinical prognosis. (5) Mean eosinophilia in the deaths was 2.6%, while 2 of the 7 deaths had 0% peripheral eosinophilia. Both of those patients had positive HTLV-1 test results and also had a history of chronic alcoholism. Eosinophils might play an important role in protecting the host against fulminant strongyloidiasis. (39) Immunomodulatory effects of HTLV-1 and the hematopoietic-suppressive effects of chronic alcoholism significantly contributed to poor eosinophilic response to Strongyloides organisms. There may also be a synergistic effect. Unlike other cases reported in the literature, (5-7, 19, 20) none of the 7 patients who died in this series were on steroid therapy. Six (86%) of the 7 patients who died were infected with HTLV-1, however, HTLV-1 contributed significantly to morbidity and mortality due to strongyloidiasis in our series. The therapeutic efficacy of thiabendazole may be red uced in HTLV-1 infection. (40) One patient with chronic alcoholism and no other identifiable risk factor died from Klebsiella pneumonia with septicemia. Death was rapid, occurring within 24 hours of onset of fever and respiratory distress. Gram-negative bronchopneumonia due to Strongyloides infection should be considered in alcoholic patients from endemic areas with fever and respiratory distress.

CONCLUSION

Physicians should be familiar with the common and unusual presentations of this rare but fatal condition, as well as the various underlying predisposing diseases. The indicators of poor prognosis in this study were sepsis, prerenal azotemia, eosinopenia, HTLV-1 infection, and chronic alcoholism.

TABLE 1

Clinical Characteristics at Presentation in Hyperinfective
Strongyloidiasis

        Characteristics          No. of Patients (%)

Gastrointestinal                       21 (78)
Weight loss                            19 (70)
Recurrent bronchopneumonia              3 (11)
Asthma-like illness                     1 (4)
Anemia                                 17 (63)
Hypoproteinemia/hypoalbuminemia        18 (67)
Renal impairment                        8 (30)
Sepsis                                  7 (26)
Eosinophilia                            8 (30)
Arthropathy                             1 (4)
Pleural effusion                        1 (4)
Occult blood in stool                  15 (56)
TABLE 2


Frequency of Gastrointestinal Symptoms in Patients With Hyperinfective
Strongyloidiasis

          Symptom            No. of Patients (%)

Diarrhea                          13 (48)
Vomiting                          10 (37)
Abdominal pain                    11 (41)
Gastrointestinal hemorrhage        6 (22)
Paralytic ileus                    1  (4)
TABLE 3

Underlying Diseases in Hyperinfective Strongloidiasis

                          Total No. of     Patients with
     Disease            Patients Assessed   Disease (%)

HTLV-1 infection               24             17 (71)
HIV infection                  27              0
Chronic alcoholism             27             12 (44)
Gastric cancer                 27              1  (4)
NHL & HTLV-1 infection         27              2  (8)
Chronic alcoholism &           24              3 (13)
 HTLV-1 infection

HTLV-1 = Human Tlymphotropic virus

HIV = human immunodeficiency virus

NHL = non-Hodgkin's lymphoma.
TABLE 4

Percent Eosinophils and Morbidity/Mortality

     Patient Cohort        No. of Patients  Mean Eosinophils (%)

All patients                     27                 4.1
HTLV-1-infected patients         17                 3.4
HTLV-1-infected & chronic         3                 0.6
 alcoholism
Chronic alcoholism only           9                 4.5
Total deaths                      7                 2.6

HTLV-1 = Human T-lymphotropic virus.

Acknowledgements. We thank the staff at Medical Laboratory Services of the Princess Margaret Hospital, Dominica, and the Caribbean Research and Epidemiology Center (CAREC) in Trinidad for the confirmatory test on HTLV-1.

References

(1.) Barr JR: Strongyloides stercoralis. Can Med Assoc J 1978; 118:933-935

(2.) Grell G, Watty E: An analysis of infection and infestations in Dominica, west Indies. West Indian Med J 1976; 25:166-176

(3.) Genta RM: Global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevention of disseminated disease. Rev Infect Dis 1989; 11:755-767

(4.) Milder JE, Walzer PD, Kilgore G, et al: Clinical features of Strongyloides stercoralis infection in an endemic area of the United States. Gastroenterology 1981;80:1481-1488

(5.) Igra-Seigman Y, Kapila R, Sen P, et al: Syndrome of hyperinfection with Strongyloides stercoralis. Rev Infect Dis 1981; 3:397-407

(6.) Leelarasamee A, Nimmannit S, Nanakorn S, et al: Disseminated Strongyloides: report of seven cases. Southeast Asian J Trop Med Public Health 1978; 9:539-542

(7.) Link L, Orenstein R: Bacterial complications of strongyloidiasis: Streptococcus bovis meningitis. South Med J 1999; 92:728-731

(8.) Owor R, Wamukota WM: A fatal case of strongyloidiasis with Strongyloides larva in the meninges. Trans R Soc Trop Med Hyg 1977; 70:497-499

(9.) Goyal SB: Intestinal strongyloidiasis manifesting as cosinophilic pleural effusion. South Med J 1998; 9:678-769

(10.) Emad A: Exudative eosinophilic pleural effusion due to Strongyloides stercoralis in a diabetic man. South Med J 1999; 92:58-60

(11.) Yee YK, Lam CS, Yung CY, et al: Strongyloides as a possible cause of nephrotic syndrome. Am J Kidney Dis 1999; 33:E4

(12.) Mori S, Konishi T, Matsuoka K, et al: Strongyloidiasis associated with nephrotic syndrome. Intern Med 1998; 37:606-610

(13.) Wong TY, Szeto CC, Lai FF, et al: Nephrotic syndrome in strongyloidiasis: remission after eradication with antihelminthic agents. Nephron 1998; 79:333-336

(14.) Kinjo T, Tsuhako K, Nakazato I, et al: Extensive intra-alveolar hemorrhage caused by disseminated strongyloidiasis. Int J Parasitol 1998; 28:323-330

(15.) Wehner JH, Kirsch CM: Pulmonary manifestations of strongyloidiasis. Semin Respir Infect 1997; 12:122-129

(16.) Bhatt BD, Cappell MS. Smilow PC, et al: Recurrent massive gastrointestinal hemorrhage due to Strongyloides stercoralis infection. Am J Gastroenterol 1990; 85:1034-1036

(17.) Bocanegra TS, Espinoza LR, Bridgeford PH, et al: Reactive arthritis induced by parasitic infection. Ann Intern Med 1981; 94:207-209

(18.) Akoglu T, Tuncer I, Erken E, et al: Parasitic arthritis induced by Strongyloides stercoralis. Ann Rheum Dis 1984; 43:523-525

(19.) Lee SK, Shuri RM, Khang SK, et al: Nine cases of strongyloidiasis in Korea. Korean J Parasitol 1994; 32:49-52

(20.) Boram LH, Keller KF, Justus DE, et al: Strongyloidiasis in immunosupressed patients. Am J Clin Pathol 1981; 76:778-781

(21.) Meyers AM, Shapiro DJ, Milne FJ, et al: Strongyloides stercoralis hyperinfection in a renal allograft recipient. S Afr Med J 1976;50:1301-1302

(22.) Devault GA Jr, King JW, Rohr MS, et al: Opportunistic infections with Strongyloides stercoralis in renal transplantation. Rev Infect Dis 1990; 12:653-671

(23.) Genta RM, Miles P. Fields K: Opportunistic Strongyloides stercoralis infection in lymphoma patients: report of a case and review of the literature. Cancer 1989;63:1407-1411

(24.) Gotuzzo E, Terashima A, Alvarz H, et al: Strongyloides stercoralis hyperinfection associated with human T-cell lymphotropic virus type-1 infection in Peru. Am J Trop Med Hyg 1999; 60:146-149

(25.) Neisson-Vernant C, Eduoard A: Malignant strongyloidiasis and the HTLV-1 virus [in French]. Rev Prat 1990; 40:2127-2128

(26.) Newton RC, Limpuamgthip P, Greenberg S, et al: Strongyloides stercoralis hyperinfection in a carrier of HTLV-1 virus with evidence of selective immunosupression. Am J Med 1992; 92:202-208

(27.) Savangarajan R, Ranganathan A, Belmonte AH, et al: Strongyloides stercoralis infection in AIDS. AIDS Patient Care STDS 1997; 11:407-414

(28.) Lessnau KD, Can S, Talavera W: Disseminated Strongyloides stercoralis in human immunodeficiency virus infected patients: treatment failure and a review of the literature. Chest 1993; 104:119-122

(29.) Maayan S, Wormser GP, Widerhorn J, et al: Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome. Am J Med 1987; 83:945-948

(30.) Ho PL, Luk WK, Chan AC, et al: Two cases of fatal strongyloidiasis in Hong Kong. Pathology 1997; 29:324-326

(31.) Arije A, Kadiri S, Osobamiro OA, et al: Chronic diarrhea due to strongyloidiasis in a Nigerian with chronic renal failure: a case report. J Trop Med Hyg 1992; 95:354-355

(32.) Screen was DV, Kumar A, Kumar YR. et al: Intestinal strongyloidiasis: a rare opportunistic infection. Indian J Gastroenterol 1997; 16:105-106

(33.) Gaburri D, Gaburri AK, Hubner E, et al: Intestinal parasitosis and hepatic cirrhosis. Arq Gastroenterol 1997; 34:7-12

(34.) Hayashi J, Kishihara Y, Yoshimura E, et al: Correlation between human T-cell lymphotropic virus type-1 and Strongyloides stercoralis infections and serum immunoglobulin E responses in residents of Okinawa, Japan. Am J Trop Med Hyg 1997; 56:71-75

(35.) McRury J, Messias IT, Walzer PD, et al: Specific IgE responses in human strongyloidiasis. J Clin Exp Immunol 1986; 65:631-638

(36.) Genta RM, Douce RW, Walzer PD: Diagnostic implications of parasite-specific immune responses in immunocompromised patients with strongyloidiasis. J Clin Microbiol 1986; 23:1099-1103

(37.) Genta RM: Dysregulation of strongyloidiasis:a new hypothesis. Clin Microbiol Rev 1992; 5:345-355

(38.) Longworth DL, Weller PF: Hyperinfection syndrome with strongyloidiasis. Curr Clin Top Infect Dis 1986; 10:1

(39.) Heyworth MF: Parasitic diseases in immunocompromised hosts. Cryptosporidiosis, isosporiasis and strongyloidiasis. Gastroenterol Clin North Am 1996; 25:691-707

(40.) Sato Y, Shiroma Y, Kiyuna S, et al: Reduced efficacy of chemotherapy might accumulate concurrent HTLV-1 infection among strongyloidiasis patients in Okinawa, Japan. Trans R Soc Trop Med Hyg 1994; 88:59

RELATED ARTICLE: KEY POINTS

* Hyperinfective strongyloidiasis is a clinical marker of HTLV-1 infection in patients from endemic regions.

* Gastrointestinal symptoms, weight loss, hypoproteinemia, and anemia are the predominant presentations and may mimic severe malnutrition or gastrointestinal malignancy in adults.

* Sepsis, prerenal azotemia, eosinopenia, and HTLV-1 infection with chronic alcoholism are indicators of a poor prognosis.

From the Departments of Medicine and Pathology, Princess Margaret Hospital, Roseau, Dominica, West Indies; and Ross University School of Medicine, Portsmouth, Dominica, West Indies.

Reprint requests to A. Olayinka Adedayo, MBBS, Princess Margaret Hospital, Roseau, Dominica, West Indies.